The goal of this research is to understand the role of immunologically triggered injury to vascular endothelium, and subsequent ischemia and infarction, in skin allograft rejection and in immune rejection of solid tumors. Studies of first and second set skin allograft rejection will be performed in mice. The role of endothelial necrosis and graft infarction will be evaluated morphologically, using 1 micrometer sections and electron microscopy, in skin grafts transplanted among strains with H-2 and non-H-2 antigenic differences of varying strength, in full thickness as opposed to pure epidermal grafts, and in Sk-alloantigen dependent skin graft rejection in radiation chimeras. Leukocyte populations or humoral components cytotoxic to endothelium will be identified both by in vivo studies of skin graft rejection in immunosuppressed or nude mice reconstituted after skin grafting with leukocytes or serum components and by in vitro studies of the cytotoxicity of defined populations of leukocytes, serum components, or lymphokines for cultured vascular endothelium. Colloidal, carbon, radioactive microspheres, and radioiodinated proteins will be used to examine relative blood flows, and changes in vascular permeability, both in mouse and/or guinea pig skin allograft rejection and in the growth and/or rejection of vascularized subcutaneous line 1 and 10 hepatomas syngeneic in strain 2 guinea pigs.